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FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be cultured from colonic mucosa of patients with Crohn's disease

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  • The Department of Hepatology and Gastroenterology V
  • The Department og Pulmunary Medicine
Summary CD4(+)CD25(+) regulatory T cells (T(regs)) are involved in the maintenance of peripheral tolerance and ensure a balanced immune response competent of fighting pathogens and at the same time recognizing commensals as harmless. This feature is lost in Crohn's disease (CD). The forkhead/winged helix transcription factor FoxP3 is a master gene for T(reg) function and defects in the FoxP3 gene lead to a clinical picture similar to inflammatory bowel disease (IBD). Murine colitis can be cured by adoptive transfer of T(regs) and ex vivo-generated gut-specific T(regs) represent an attractive option for therapy in CD. Thus, defective T(regs) could contribute to the development of CD. We cultured biopsies of colonic mucosa in the presence of high concentrations of interleukin (IL)-2 and IL-4 to overcome the anergic nature of naturally occurring CD4(+)CD25(+) T(regs) in the mucosa. We investigated the expression of FoxP3 and regulatory potential of gut-derived CD4(+)CD25(+) T cells cultured from patients with CD and healthy individuals. The FoxP3 expression was analysed by reverse transcriptase polymerase chain reaction (RT-PCR), and the suppressive effect of FoxP3(+)CD4(+)CD25(+) T cells on proliferation and cytokine production of autologous CD4(+) T cells was assessed by flow cytometry. Cultured gut-derived T cells with CD4(+)CD25(+) phenotype expressed FoxP3 and were able as the freshly isolated T(regs) from peripheral blood to suppress proliferation and cytokine production of autologous CD4(+) T cells. Thus, we demonstrate that FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be propagated in vitro from inflamed mucosa of CD patients, which may be of interest in adoptive immunotherapy.
Original languageEnglish
JournalClinical and Experimental Immunology
Volume141
Issue3
Pages (from-to)549-57
Number of pages8
ISSN0009-9104
DOIs
Publication statusPublished - 2005

    Research areas

  • Adult, CD4-Positive T-Lymphocytes, Case-Control Studies, Cells, Cultured, Colon, Crohn Disease, DNA-Binding Proteins, Down-Regulation, Female, Flow Cytometry, Forkhead Transcription Factors, Humans, Interferon-gamma, Interleukin-2, Interleukin-4, Intestinal Mucosa, Male, RNA, Messenger, Receptors, Interleukin-2, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha

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